Immune-related intestinal chloride secretion. II. Effect of adenosine on T84 cell line
The inflammatory mediator adenosine caused sustained Cl-secretion across monolayers of T84 cells. The effect was promptly reversed by the adenosine receptor antagonist 8-phenyltheophylline and appeared to be mediated through an adenosine A2-receptor [rank order of potency: 5'-(N-ethyl)-carboxamido-adenosine (NECA) > adenosine > (-)-N6-(phenylisopropyl)adenosine (PIA) ≥ (+)-PIA]. High doses of adenosine and its analogues increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) but not guanosine 3',5'-cyclic monophosphate (cGMP) or free cytosolic Ca2+. However, lower concentrations of adenosine had maximal effects on Cl-secretion with little or no effect on cAMP. In other respects, Cl-secretion resembled that induced by cAMP-mediated secretagogues such as vasoactive intestinal peptide (VIP). Addition of both low and high doses of NECA activated basolateral K+and apical Cl-channels, exhibited synergism with Ca2+-mediated secretagogues, did not produce additive effects with VIP or Escherichia coli heat-stable enterotoxin, and was associated with cAMP-dependent protein kinase-mediated protein phosphorylation. The results suggest that either adenosine mobilizes an intracellular pool of cAMP that is extremely efficiently coupled to the cAMP-dependent protein kinase and is thereafter rapidly destroyed or that second messenger(s) other than cAMP, cGMP, or Ca2+are able to activate Cl-secretion in the T84 cell line. In the latter case, such messenger(s), as yet unidentified, might represent a final common pathway for cyclic nucleotide-activated Cl-secretion.
Barrett, KE; Cohn, JA; Huott, PA; Wasserman, SI; Dharmsathaphorn, K
Volume / Issue
International Standard Serial Number (ISSN)